NEURODEFENSE Informe resumido

The ability to control our social behavior is essential for almost every social interaction. It frequently fails in challenging situations when people fall back on basic defensive ‘freeze-fight-flight’ (FFF) reactions. It chronically fails in social motivational disorders, with social anxiety as one extreme, and aggression as another. Such disorders are notoriously resistant to therapy. Therefore the current project aims to shed mechanistic insight into the psychological and neurobiological control of human FFF behaviour and its development.

Project 1 aims to develop new methods to study human FFF and the transition from freezing to fight-or-flight, in particular. We have developed a FFF-shooting task that successfully quantifies individual differences in freezing and the transition to active fight-flight in terms of psychophysiology and in terms of decision making (Gladwin ea, under revision). We found that aggressive people show less freezing (less parasympathetically driven fear bradicardia and immobility) under conditions of threat of shock and faster transition to sympathetic fight mode (shooting). In addition we observed that freezing is stronger in the context of action preparation.

Project 2 aims to test underlying neuroendocrine mechanisms of FFF control and to shed mechanistic insight on those mechanisms by direct brain stimulation and hormonal (testosterone) interventions. We adapted the FFF shooting task for fMRI and as predicted, we found that fear bradycardia, signalling parasympathetic response of freezing, was associated with increased activity in a brainstem structure called the periaqueductal gray (brainstem) and in the amygdala. Moreover, the transition to sympathetic fight was associated with increased frontal activity (Hashemi ea, in prep). These findings confirm our hypothesis that humans, alike animals activate subcortical brain regions during defensive stress behaviours. In addition we were able to directly influence automatic action tendencies by transcranial direct current stimulation (tDCS) over the frontal cortex, which resulted in decreased transfer from automatic affect to instrumental avoidance (Ly ea, submitted). And by testosterone administration promoting threat approach in healthy and in socially anxious (Radke ea, 2015, Science Advances; Enter ea, PNEC). The latter studies gave rise to new collaborative, studies exploring therapy enhancing effects of testosterone administration during exposure treatment in patients with social anxiety disorder.

Project 3 aims to predict the onset of anxiety & aggressive symptoms by automatic FFF in a prospective study. To investigate the development of FFF tendencies in a longitudinal fashion, several FFF tasks have been assessed in adolescents of the Nijmegen Longitudinal Study (NLS) at Age 14 and Age 17. At Age 14 we observed that frontal control over automatic action tendencies develops as a function of pubertal stage (Tyborowska ea, under revision). These findings provide a starting point for investigating the development of emotional action control across time and in relation to genetic and environmental factors.

Overall, this project is already increasing our knowledge of human defensive responses, with both theoretical and practical relevance. The innovative approach is enhancing theoretical accounts by constraining models based on the underlying neurobiology and endocrinology, and has been giving rise to new human-animal translational projects and clinically oriented projects.